Attempts have long been made to incorporate pharmaceutically active agents into chewing gum as a means of administering the active agent to the subject. Traditionally, these efforts have employed common chewing gum production techniques wherein a gum base is heated until it becomes a viscous or fluid mass. Additional components (such as flavors or active ingredients) then blended into the gum base. Finally, the mixture is cooled, pressed and cut to produce the final product.
Alternatively, the various components are blended in a gum slurry that is coagulated before pressing into the final product form.
However, many pharmaceutically active agents possess unpleasant taste or odor characteristics which were all too apparent when mixing with gum by the above method, resulting in undesirable chewing gum products. Many active agents also tend to irritate the mucosas. Still other pharmaceutically active agents degrade rapidly, making it impractical to include them in chewing gum.
Another problem with known methods is that the gum base is heated to a fluid mass to facilitate mixing of other ingredients. Such elevated temperatures can cause degradation of heat-sensitive compounds, including active agents and flavors.
Prior art attempts to overcome these difficulties included the following: to avoid the degradation of the active agents, chewing gum was cold-produced by direct compression of the ingredients; to obtain the ability to retard or control the release rate of active agents, the active agents were formulated into microcapsules. However, microencapsulation technology is complex and costly often resulting in retarded release products. It is therefore not well-adapted for drugs for which rapid absorption through the oral mucosas is necessary or desirable.
In addition, known processes for medicated gum preparations often utilize organic solvents to dissolve the active agents. It is well known that these organic solvents are difficult to eliminate from the final product and may present certain health risks if even trace amounts remain in the final dosage form. Additionally, use of organic solvents in connection with industrial processes is becoming increasingly unpopular due to health and environmental considerations (e.g., risks attendant to exposure of personnel and problems in effecting proper disposal of waste solvents).
Water has also been utilized in gum preparations, but it is difficult to eliminate, especially at the relatively low temperatures that are desirable for production of chewing gum. Heating the gum mass to eliminate water is not advisable, because the gum will then become more sticky which makes handling difficult and interferes with large-scale, semi- or totally automated production.
Thus, the problems of realizing a medicated chewing gum produced by direct compression, with immediate or rapid release of the active agent and efficient masking of unpleasant organoleptic characteristics of active agents, remained unsolved.
The properties of cyclodextrin in forming inclusion complexes have been recognized and some of the difficulties recounted above were solved by applying these techniques. It was found that certain compounds could be included within cyclodextrins and then blended into a gum base under traditional chewing gum production methods. The compounds were then released upon chewing. See, for example, U.S. Pat. No. 5,165,943 to Patel et al.
Although these methods helped to mask the unpleasant taste of certain compounds and reduce degradation, there were still significant shortcomings. Water and stickiness are still problems, and the methods known in the art do not address the temperature sensitivity of certain active agents.